Nishimura Y, Kanai T, Oiso M, Tabata H, Ito H, Kira J, Chen Y Z, Matsushita S
Department of Neuroscience and Immunology, Kumamoto University Graduate School of Medical Sciences, Japan.
Int J Cardiol. 1998 Oct 1;66 Suppl 1:S93-104; discussion S105. doi: 10.1016/s0167-5273(98)00156-9.
It is well known that individuals positive for particular HLA-class II alleles show high risks for the development of Takayasu arteritis and other diseases caused by immunological disorders such as autoimmune diseases and allergies. HLA class II molecules present antigenic peptides to CD4+ T cells. Their extensive polymorphism affects the structures of peptides bound to HLA class II molecules to create individual differences in immune responses to antigenic peptides. To better understand the mechanisms for association between HLA class II alleles and susceptibility to autoimmune diseases, it is important to identify self-peptides presented by disease-susceptible HLA class II molecules and triggering disease-causative T cells. Many autoimmune diseases are observed in all ethnic groups, whereas the incidences of diseases, clinical manifestations and disease-susceptible HLA class II alleles are different among various ethnic groups for some autoimmune diseases. These phenomena suggest that differences in autoimmune self-peptide(s) in the context of disease-susceptible HLA class II molecules may cause these differences. Therefore, comparisons among disease-susceptible HLA class II alleles, autoimmune self-peptides and clinical manifestations of autoimmune diseases in different ethnic groups would be helpful in determining the pathogenesis of the diseases. In this paper, we describe our recent findings on: (1) the uniqueness of both clinical manifestations and HLA-linked genetic background of Asian-type (optico-spinal form) multiple sclerosis; (2) the structural characteristics of peptides bound to HLA-DQ molecules susceptible to insulin-dependent diabetes mellitus; (3) the identification of a disease-related autoantigenic peptide presented by disease-susceptible HLA-DQ molecules in Asians-specific infant onset myasthenia gravis; and (4) a manipulation of human T cell response by altered peptide ligands, as a possible candidate for new and antigen-specific immuno-suppressive therapy against autoimmune diseases.
众所周知，特定HLA - II类等位基因呈阳性的个体患大动脉炎以及其他由免疫紊乱引起的疾病（如自身免疫性疾病和过敏）的风险很高。HLA - II类分子将抗原肽呈递给CD4 + T细胞。它们广泛的多态性影响与HLA - II类分子结合的肽的结构，从而在对抗原肽的免疫反应中产生个体差异。为了更好地理解HLA - II类等位基因与自身免疫性疾病易感性之间的关联机制，识别由疾病易感的HLA - II类分子呈递并触发致病T细胞的自身肽非常重要。所有种族群体中都观察到许多自身免疫性疾病，然而，对于某些自身免疫性疾病，不同种族群体的疾病发病率、临床表现和疾病易感的HLA - II类等位基因存在差异。这些现象表明，在疾病易感的HLA - II类分子背景下自身免疫性自身肽的差异可能导致了这些不同。因此，比较不同种族群体中疾病易感的HLA - II类等位基因、自身免疫性自身肽和自身免疫性疾病的临床表现，将有助于确定疾病的发病机制。在本文中，我们描述了我们最近的研究发现：（1）亚洲型（视神经脊髓型）多发性硬化症的临床表现和HLA相关遗传背景的独特性；（2）与胰岛素依赖型糖尿病易感的HLA - DQ分子结合的肽的结构特征；（3）在亚洲人特有的婴儿型重症肌无力中，由疾病易感的HLA - DQ分子呈递的与疾病相关的自身抗原肽的鉴定；（4）通过改变肽配体对人类T细胞反应的调控，作为针对自身免疫性疾病的新型抗原特异性免疫抑制疗法的可能候选方法。
